Laparoscopic management of fallopian tube carcinoma with paraneoplastic cerebellar degeneration
© Springer-Verlag Berlin / Heidelberg 2006
Received: 25 February 2006
Accepted: 8 June 2006
Published: 1 August 2006
An asymptomatic tumor of the fallopian tube with elevation of serum CA125 concentration was found in a 75-year-old woman during a search for primary malignancy that was causing paraneoplastic cerebellar degeneration with a positive anti-Yo antibody. Since there were no apparent metastatic lesions detected by image diagnostic procedures, a diagnosis of early fallopian tube carcinoma was made preoperatively. After confirmation of the presence of a left tubal tumor without apparent invasion to the adjacent organs and peritoneal metastasis, laparoscopic salpingo-oophorectomy was subsequently performed. The histopathological diagnosis was of moderately differentiated serous adenocarcinoma of the fallopian tube with marked plasma cell infiltration. After surgery, the CA125 value immediately decreased, and there was no evidence of tumor recurrence noted thereafter. The patient died 51 months after surgery due to progression of neurological symptoms.
Primary fallopian tube carcinoma is an uncommon malignancy that accounts for approximately 0.3% of all gynecological cancers and typically affects postmenopausal women . Furthermore, on extremely rare occasions [2–4], fallopian tube carcinoma is known to associate with paraneoplastic cerebellar degeneration (PCD), which is a remote complication of malignant tumor without any relation to metastasis, malnutrition or damage due to chemotherapy [5, 6]. This disorder evolves clinically as progressive ataxia, dysarthria, and nystagmus, and pathologically as extensive loss of cerebellar Purkinje cells . The presence of anti-Yo antibody directed against Yo antigens shared by Purkinje cells and tumor cells in serum and cerebrospinal fluid of the patients suggests an autoimmune mechanism for this disorder . Since the onset of cerebellar dysfunction usually precedes the manifestation of cancer-related symptoms by many months , extensive search for occult primary malignancy is essentially important for early diagnosis and treatment of cancer in cases of PCD.
In this paper, we present a rare case of anti-Yo antibody-positive PCD with asymptomatic fallopian tube carcinoma that was successfully diagnosed and managed by laparoscopy.
The excised specimen was histopathologically examined. The main solid tumor was at the distal portion of the tube, while the proximal portion of the tube showed hydrosalpinx containing dark red fluid (Fig. 3b). Ovarian tissue was atrophic, and there were no malignant findings. The tumor in the fallopian tube was diagnosed as a moderately differentiated serous adenocarcinoma with marked plasma cell infiltration, which is a frequently observed phenomenon in PCD-related tumor tissue  (Fig. 3c). Although the tumor extended into the muscularis, there was no invasion to the serosal surface.
After surgery, the CA125 value immediately decreased, indicating successful removal of the fallopian tube carcinoma. There was no evidence to suggest tumor recurrence thereafter. However, anti-Yo antibody persisted and neurological symptoms gradually worsened. Two years after surgery, the patient became bedridden and died 51 months later due to progression of neurological symptoms. Autopsy was not permitted by the family.
PCD is a rare remote effect of malignant tumor [5, 6] that is characterized clinically by evolving cerebellar dysfunction and histopathologically by widespread loss of cerebellar Purkinje cells. Evidence is accumulating that patients with PCD have a particular autoantibody referred to as anti-Yo antibody (also known as anti-Purkinje cell antibody) that possesses cross-reactivity to the Yo antigen of tumor cells as well as Purkinje cells . Although the pathogenesis of PCD remains unclear, it has been hypothesized that cerebellar degeneration is a result of an autoimmune-induced destruction of Purkinje cell function by anti-Yo antibody generated against cross-reactive tumor cell Yo antigen .
In patients with anti-Yo antibody-positive PCD, gynecological malignancies are known to be frequently associated [5, 6]. The majority of these cases involve ovarian cancer, and, on rare occasions, tubal carcinoma is known to be associated with PCD [2–4]. Two approaches can be used to treat paraneoplastic neurologic syndrome . The first treatment is directed toward the underlying tumor, while the second approach focuses on the autoimmune disease causing the cerebellar dysfunction. For the neurologist, paraneoplastic syndrome is a therapeutic challenge, and medical treatment for paraneoplastic syndrome is generally unsatisfactory . Therefore, early tumor detection and treatment by a gynecologist should be the primary objective in these patients. According to a review  of long-term clinical outcomes in cases of anti-Yo antibody-associated PCD, cancer progression was the cause of death in almost half of the patients, including a patient with advanced cancer. Most of these cancer-related deaths were due to the delay in diagnosis of the primary malignancy, and patients with early stage cancer showed a relatively favorable cancer-related prognosis. Manifestation of cerebellar dysfunction usually precedes the onset of symptoms of the primary malignancy by many months . Therefore, early screening of anti-Yo antibody in patients with cerebellar degeneration is an important step before one initiates an extensive search for the primary tumor to achieve improvement of cancer-related prognosis in PCD patients. Further, it is known that the presence of anti-Yo antibody is important to predict the cancer-related prognosis of patients, since tumor progression in PCD patients with anti-Yo antibody is slower than usual , probably due to the suppression of tumor growth through antibody-mediated immune mechanisms by massive infiltrating inflammatory cells, as shown in the present case. Thus, the preoperative evaluation of cancer metastasis and invasion to local structures that drastically decreases the possibility of tumor control  should be carefully pursued before the treatment strategy for the individual case is developed.
Unfortunately, early detection and even cure of the cancer underlying PCD usually does not affect neurological symptoms in most cases, since cerebellar dysfunction stabilizes in the early stage after symptom onset before the cancer has been diagnosed and treatment initiated [5, 6]. This was also true in our patient, as anti-Yo antibody persisted even after the CA125 level had decreased and, without apparent recurrence of cancer, the neurological symptoms gradually worsened. However, cases in which the symptoms of cerebellar degeneration either improve or stabilize have also been reported . Thus, early detection and treatment of the primary malignancy may contribute to improving the neurological prognosis in some patients as well as decreasing the incidence of cancer-related death.
When PCD-related primary gynecological malignancies are found, exploratory laparotomy has been traditionally chosen for diagnosis and treatment [2, 5, 6]. However, this more invasive treatment may worsen the general condition of a patient with cerebellar dysfunction. Along with advances in operative laparoscopic procedures and surgical equipment, recent advances in image diagnostic procedures  have facilitated the accurate evaluation of primary tumor and the presence of metastases. Therefore, if apparent metastatic regions are not recognized and early stage of primary malignancy is assumed preoperatively, as in the present case, a laparoscopic approach could be a less invasive procedure to diagnose and further treat the primary cancer in a patient showing a relatively poor condition due to cerebellar dysfunction.
Further study is necessary to clarify the indications for laparoscopic treatment of primary malignancy in patients with PCD by accumulating additional cases. Both neurologists and gynecologists need to have sufficient knowledge of this rare disorder in order to improve the prognosis of PCD patients by early detection and treatment of the primary malignancy.
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